Variant 6-96889661-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014165.4(NDUFAF4):c.*1443G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,376 control chromosomes in the GnomAD database, including 4,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4532 hom., cov: 32)

Exomes 𝑓: 0.18 ( 3 hom. )

Consequence

NDUFAF4
NM_014165.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.475

Variant links:

Genes affected

NDUFAF4 (HGNC:21034): (NADH:ubiquinone oxidoreductase complex assembly factor 4) NADH:ubiquinone oxidoreductase (complex I) catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. This gene encodes a complex I assembly factor. Mutations in this gene are a cause of mitochondrial complex I deficiency. [provided by RefSeq, Oct 2009]

NDUFAF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 6-96889661-C-T is Benign according to our data. Variant chr6-96889661-C-T is described in ClinVar as [Benign]. Clinvar id is 358249.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDUFAF4	NM_014165.4 linkuse as main transcript	c.*1443G>A		3_prime_UTR_variant	3/3	ENST00000316149.8	NP_054884.1	Q9P032

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDUFAF4	ENST00000316149 linkuse as main transcript	c.*1443G>A		3_prime_UTR_variant	3/3	1	NM_014165.4	ENSP00000358272.4		Q9P032

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36703

AN:

151854

Hom.:

4530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.235

GnomAD4 exome

AF:

0.185

AC:

AN:

406

Hom.:

Cov.:

AF XY:

0.179

AC XY:

AN XY:

246

show subpopulations

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.500

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.242

AC:

36720

AN:

151970

Hom.:

4532

Cov.:

AF XY:

0.243

AC XY:

18037

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.327

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.239

Alfa

AF:

0.233

Hom.:

774

Bravo

AF:

0.251

Asia WGS

AF:

0.315

AC:

1096

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Mitochondrial complex I deficiency, nuclear type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over